The objective of this project is to provide information on metabolic changes occurring in nuclei of pancreatic tissue exposed to carcinogens. The initial studies indicated that exposure to 7,12-dimethylbenzanthracene (DMBA) resulted in alterations in content of DNA and RNA for periods up to 35 hours after exposure. Protein synthesis was also depressed during this same time period. During this reporting period we measured the rate of RNA synthesis as reflected by the uptake of radiolabeled uridine. These studies demonstrated that RNA synthesis was altered in a biphasic response, in parallel with the changes in RNA content, and that changes in synthesis preceded the maxima and minima of RNA content. Preliminary studies with benzopyrene (BP) indicated that only the initial change in synthesis of RNA was observed following BP treatment. The reason for the difference between carcinogens is presently unknown. We have measured changes in the DNA-dependent RNA polymerase enzyme activity during the same period of time and observed that changes in rates of polymerase enzyme activity were in parallel with the changes in uridine uptake. Ribonuclease enzyme activity and ribonuclease enzyme inhibitor activity were measured concurrently with the polymerase enzyme activity. The enzyme and inhibitor activities demonstrated changes that were in parallel with ribonuclease activity which suggested that the RNA content was not significantly affected by ribonuclease enzyme activity. These studies showed that DMBA significantly affected RNA synthesis, but they could not distinguish between changes in the polymerase enzyme content, an effect on DNA template, or an effect on some rate-limiting enzyme or cofactor. There are reports in the literature which demonstrate the rate-limiting effect of ornithine decarboxylase on RNA synthesis. Studies measurng the change in ornithine decarboxylase following DMBA treatment are underway.